Bad Science (11 page)

But free radicals in the wrong places can damage the desirable components of cells. They can damage the lining of your arteries, and they can damage DNA, and damaged DNA leads to aging or cancer, and so on. For this reason, it has been suggested that free radicals are responsible for aging and various diseases. This is a theory, and it may or may not be correct.

Antioxidants are compounds which can—and do—“mop up” these free radicals, by reacting with them. If you look at the vast, interlocking flowchart diagrams of how all the molecules in your body are metabolized from one form to the next, you can see that this is happening all over the shop.

The theory that antioxidants are protective is separate from, but builds upon, the free radical theory of disease. If free radicals are dangerous, the argument goes, and antioxidants on the big diagrams are involved in neutralizing them, then eating more antioxidants should be good for you and reverse or slow aging and prevent disease.

There are a number of problems with this as a theory. First, who says free radicals are always bad? If you’re going to reason just from theory, and from the diagrams, then you can hook all kinds of things together and make it seem as if you’re talking sense. As I said, free radicals are vital for your body to kill off bacteria in phagocytic immune cells, so should you set yourself up in business and market an antioxidant-
free
diet for people with bacterial infections?

Second, just because antioxidants are involved in doing something good, why should eating more of them necessarily make that process more efficient? I know it makes sense superficially; but so do a lot of things, and that’s what’s really interesting about science (and this story in particular): sometimes the results aren’t quite what you might expect. Perhaps an excess of antioxidants is simply excreted or turned into something else. Perhaps it just sits there doing nothing, because it’s not needed. After all, half a tank of gasoline will get you across town just as easily as a full tank. Or perhaps, if you have an unusually enormous amount of antioxidant lying around in your body doing nothing, it doesn’t just do nothing. Perhaps it does something actively harmful. That would be a turnup for the books, wouldn’t it?

There were a couple of other reasons why the antioxidant theory seemed like a good idea twenty years ago. First, when you take a static picture of society, people who eat lots of fresh fruits and vegetables tend to live longer and have less cancer and heart disease, and there are lots of antioxidants in fruit and vegetables (although there are lots of other things in them too, and, you might rightly assume, lots of other healthy things about the lives of people who eat lots of healthy fresh fruit and vegetables, like their posh jobs, moderate alcohol intake, etc.).

Similarly, when you take a snapshot picture of the people who take antioxidant supplement pills, you will often find that they are healthier or live longer: but again (although nutritionists are keen to ignore this fact), these are simply surveys of people who have already chosen to take vitamin pills. These are people who are more likely to care about their health and are different from the everyday population—and perhaps from you—in lots of other ways, far beyond their vitamin pill consumption: they may take more exercise, have more social supports, smoke less, drink less, and so on.

But the early evidence in favor of antioxidants was genuinely promising and went beyond mere observational data on nutrition and health; there were also some very seductive blood results. In 1981 Richard Peto, one of the most famous epidemiologists in the world, who shares the credit for discovering that smoking causes 95 percent of lung cancer, published a major paper in
Nature
. He reviewed a number of studies that apparently showed a positive relationship between having a lot of beta-carotene on board (this is an antioxidant available in the diet) and a reduced risk of cancer.

This evidence included case-control studies, in which people
with
various cancers were compared with people
without
cancer (but matched for age, social class, gender, and so on), and it was found that the cancer-free subjects had higher plasma carotene. There were also prospective cohort studies, in which people were classified by their plasma carotene level at the beginning of the study, before any of them had cancer, and then followed up for many years. These studies showed twice as much lung cancer in the group with the lowest plasma carotene, compared with those with the highest level. It looked as if having more of these antioxidants might be a very good thing.

Similar studies showed that higher plasma levels of antioxidant vitamin E were related to lower levels of heart disease. It was suggested that vitamin E status explained much of the variations in levels of ischemic heart disease between different countries in Europe, which could not be explained by differences in plasma cholesterol or blood pressure.

But the editor of
Nature
was cautious. A footnote was put onto the Peto paper that read as follows: “Unwary readers (if such there are) should not take the accompanying article as a sign that the consumption of large quantities of carrots (or other dietary sources of beta-carotene) is necessarily protective against cancer.” It was a very prescient footnote indeed.

The Antioxidant Dream Unravels

Whatever the shrill alternative therapists may say, doctors and academics have an interest in chasing hints that could bear fruit, and compelling hypotheses like these, which could save millions of lives, are not taken lightly. These studies were acted upon, with many huge trials of vitamins set up and run around the world. There’s also an important cultural context for this rush of activity that cannot be ignored: it was the tail end of the golden age of medicine. Before 1935 there weren’t too many effective treatments around: we had insulin, liver for iron-deficiency anemia, and morphine—a drug with superficial charm at least—but in many respects, doctors were fairly useless. Then suddenly, between about 1935 and 1975, science poured out a constant stream of miracles.

Almost everything we associate with modern medicine happened in that time: treatments like antibiotics, dialysis, transplants, intensive care, heart surgery, almost every drug you’ve ever heard of, and more. As well as the miracle treatments, we really were finding those simple, direct, hidden killers that the media still pine for so desperately in their headlines. Smoking, to everybody’s genuine surprise—one single risk factor—turned out to cause almost all lung cancer. And asbestos, through some genuinely brave and subversive investigative work, was shown to cause mesothelioma.

The epidemiologists of the 1980s were on a roll, and they believed that they were going to find lifestyle causes for all the major diseases of humankind. A discipline that had got cracking when John Snow took the handle off the Broad Street pump in 1854, terminating that pocket of the Soho cholera epidemic by cutting off the supply of contaminated water (it was a bit more complicated than that, but we don’t have the time here), was going to come into its own. They were going to identify more and more of these one-to-one correlations between exposures and disease, and in their fervent imaginations, with simple interventions and cautionary advice they were going to save whole nations of people. This dream was very much not realized, as it turned out to be a bit more complicated than that.

Two large trials of antioxidants were set up after Peto’s paper (which rather gives the lie to nutritionists’ claims that vitamins are never studied because they cannot be patented: in fact, there have been a great many such trials, although the food supplement industry, estimated by one report to be worth over fifty billion dollars globally, rarely deigns to fund them). One was in Finland, where thirty thousand participants at high risk of lung cancer were recruited, and randomized to receive beta-carotene, vitamin E, or both or neither. Not only were there more lung cancers among the people receiving the supposedly protective beta-carotene supplements, compared with placebo, but this vitamin group also had more deaths overall, from both lung cancer and heart disease.

The results of the other trial were almost worse. It was called the Carotene and Retinol Efficacy Trial, or CARET, in honor of the high carotene content of carrots. It’s interesting to note, while we’re here, that carrots were the source of one of the great disinformation coups of World War II, when the Germans couldn’t understand how our pilots could see their planes coming from huge distances, even in the dark. To stop them from trying to work out if we’d invented anything clever like radar (as we had), the British instead started an elaborate and entirely made-up nutritionist rumor. Carotenes in carrots, they explained, are transported to the eye and converted to retinal, which is the molecule that detects light in the eye (this is basically true and is a plausible mechanism, like those we’ve already dealt with), so, went the story, doubtless with much chortling behind their excellent RAF mustaches, we have been feeding our chaps huge plates of carrots, to jolly good effect.

Anyway. Two groups of people at high risk of lung cancer were studied: smokers, and people who had been exposed to asbestos at work. Half were given beta-carotene and vitamin A, while the other half got placebo. Eighteen thousand participants were due to be recruited throughout its course, and the intention was that they would be followed up for an average of six years; but in fact, the trial was terminated early, because it was considered unethical to continue it. Why? The people having the antioxidant tablets were 46 percent more likely to die from lung cancer, and 17 percent more likely to die of any cause,
¹⁰
than the people taking placebo pills. This is not news, hot off the presses; it happened well over a decade ago.

Since then the placebo-controlled trial data on antioxidant vitamin supplements has continued to give negative results. The most up-to-date Cochrane reviews of the literature pool together all the trials on the subject, after sourcing the widest possible range of data using the systematic search strategies described above (rather than cherry-picking studies to an agenda); they assess the quality of the studies and then put them all into one giant spreadsheet to give the most accurate possible estimate of the risks of benefits, and they show that antioxidant supplements are either ineffective or perhaps even actively harmful.

The Cochrane review on preventing lung cancer pooled data from four trials, describing the experiences of more than one hundred thousand participants and found no benefit from antioxidants, and indeed an increase in risk of lung cancer in participants taking beta-carotene and retinol together. The most up-to-date systematic review and meta-analysis on the use of antioxidants to reduce heart attacks and stroke looked at vitamin E, and separately beta-carotene, in fifteen trials, and found no benefit for either. For beta-carotene, there was a small but significant increase in death.

Most recently, a Cochrane review looked at the number of deaths, from any cause, in all the placebo-controlled randomized trials on antioxidants that have ever been performed (many of which looked at quite high doses, but perfectly in line with what you can buy in health food stores), describing the experiences of 230,000 people in total. This showed that overall, antioxidant vitamin pills do not reduce deaths, and in fact, they may increase your chance of dying.

Where does all this leave us? There was an observed correlation between low blood levels of these antioxidant nutrients and a higher incidence of cancer and heart disease, and a plausible mechanism for how they could have been preventive, but when you gave them as supplements, it turned out that people were no better off or were possibly
more
likely to die. That is, in some respects, a shame, as nice quick fixes are always useful, but there you go. It means that something funny is going on, and it will be interesting to get to the bottom of it and find out what.

More interesting is how uncommon it is for people even to be aware of these findings about antioxidants. There are various reasons why this has happened. First, it’s an unexpected finding, although in that regard antioxidants are hardly an isolated case. Things that work in theory often do not work in practice, and in such cases we need to revise our theories, even if it is painful. Hormone replacement therapy seemed like a good idea for many decades, until the follow-up studies revealed the problems with it, so we changed our views. And calcium supplements once looked like a good idea for osteoporosis, but now it turns out that they probably increase the risk of heart attacks in older women, so we change our view.

It’s a chilling thought that when we think we are doing good, we may actually be doing harm, but it is one we must always be alive to, even in the most innocuous situations. The pediatrician Dr. Benjamin Spock wrote a record-breaking bestseller titled
Baby and Child Care
, first published in 1946, that was hugely influential and largely sensible. In it, he confidently recommended that babies should sleep on their tummies. Dr. Spock had little to go on; but we now know that this advice is wrong, and the apparently trivial suggestion contained in his book, which was so widely read and followed, has led to thousands, and perhaps even tens of thousands, of avoidable crib deaths. The more people are listening to you, the greater the effects of a small error can be. I find this simple anecdote deeply disturbing.

But of course, there is a more mundane reason why people may not be aware of these findings on antioxidants, or at least may not take them seriously, and that is the phenomenal lobbying power of a large, sometimes rather dirty industry, which sells a lifestyle product that many people feel passionately about. The food supplement industry has engineered itself a beneficent public image, but this is not borne out by the facts. First, there is essentially no difference between the vitamin industry and the pharmaceutical and biotech industries (that is one message of this book, after all: the tricks of the trade are the same the world over). Key players include companies like Roche and Sanofi-Aventis; BioCare, the U.K. vitamin pill company, is part owned by Elder Pharmaceuticals, and so on. The vitamin industry is also—amusingly—legendary in the world of economics as the setting of the most outrageous price-fixing cartel ever documented. During the 1990s the main offenders were forced to pay
the largest criminal fines ever levied in legal history
—$1.5 billion in total—after entering guilty pleas with the U.S. Department of Justice and regulators in Canada, Australia, and the European Union. That’s quite some cozy cottage industry.